Pain is generally divided into nociceptive and neuropathic pain. Nociceptive pain stems from neural pathways in response to tissue damaging or potentially tissue damaging signals, and includes inflammatory pain. Neuropathic pain tends to relate to dysfunctions within the nervous system. Unfortunately, agents that treat one kind of pain do not necessarily treat the other. Neuropathic pain is distinguished from inflammatory pain in that it is not mediated by arachidonic acid, cyclooxygenases and prostaglandins. Therefore, neuropathic pain is not reduced or alleviated by non-steroidal anti-inflammatory agents, e.g., inhibitors of cyclooxygenases (“COX”), including selective COX-2 inhibitors.
Until today, the pharmacological agents that have most commonly been shown to effectively block neuropathic pain are tricyclic anti-depressants (TCAs). However these agents are not effective at all in some patients and are only partially effective in others. TCAs have many disadvantages well known in the field. Since neuropathic pain is a debilitating and hard to treat condition, however, TCAs have been used despite their disadvantages in the absence of agents with less adverse effects.
Therefore the therapy of neuropathic pain is an unmet and growing clinical need.
It was recently shown that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. Accordingly, FXYD2 was considered as a novel specific marker restricted exclusively to said mechanoreceptors and nociceptors of primary somato-sensory neurons (Ventéo et al, 2012).